Richerson George B, Wu Yuanming
Department of Neurology, Yale University School of Medicine, New Haven 06520, USA.
J Neurophysiol. 2003 Sep;90(3):1363-74. doi: 10.1152/jn.00317.2003.
Many electrophysiologists view neurotransmitter transporters as tiny vacuum cleaners, operating continuously to lower extracellular neurotransmitter concentration to zero. However, this is not consistent with their known behavior, instead only reducing extracellular neurotransmitter concentration to a finite, nonzero value at which an equilibrium is reached. In addition, transporters are equally able to go in either the forward or reverse direction, and when they reverse, they release their substrate in a calcium-independent manner. Transporter reversal has long been recognized to occur in response to pathological stimuli, but new data demonstrate that some transporters can also reverse in response to physiologically relevant stimuli. This is consistent with theoretical calculations that indicate that the reversal potentials of GABA and glycine transporters are close to the resting potential of neurons under normal conditions and that the extracellular concentration of GABA is sufficiently high when the GABA transporter is at equilibrium to tonically activate high-affinity extrasynaptic GABAA receptors. The equilibrium for the GABA transporter is not static but instead varies continuously as the driving force for the transporter changes. We propose that the GABA transporter plays a dynamic role in control of brain excitability by modulating the level of tonic inhibition in response to neuronal activity.
许多电生理学家将神经递质转运体视为微型真空吸尘器，持续运作以将细胞外神经递质浓度降至零。然而，这与它们已知的行为并不一致，实际上只是将细胞外神经递质浓度降低到一个有限的非零值并达到平衡。此外，转运体能够同样有效地正向或反向运行，当它们反向运行时，会以不依赖钙的方式释放其底物。长期以来人们都认识到转运体反转是对病理刺激的反应，但新数据表明，一些转运体也能对生理相关刺激做出反转反应。这与理论计算结果一致，该计算表明，在正常情况下，GABA和甘氨酸转运体的反转电位接近神经元的静息电位，并且当GABA转运体处于平衡状态时，细胞外GABA浓度足够高，足以持续激活高亲和力的突触外GABAA受体。GABA转运体的平衡并非静态，而是会随着转运体驱动力的变化而持续变化。我们认为，GABA转运体通过响应神经元活动调节紧张性抑制水平，在控制大脑兴奋性方面发挥动态作用。
